This invention relates generally to nanoparticle compositions which form stable aqueous suspensions, particularly nanoparticle compositions based on transition metal oxides. Such nanoparticle compositions are useful for a variety of applications including diagnostic imaging.
Nanoparticles, i.e. particles whose diameters are appropriately measured in nanometers, have been considered for a wide variety of end uses. Some of the uses require a substantial degree of hydrophilicity. However, in a number of instances, the material upon which nanoparticles are based may lack this attribute. For instance, nanoparticles with appropriate imaging properties for use as contrast agents for MR and/or X-ray imaging are typically based on transition metal oxides which lack the level of hydrophilicity required to form the stable aqueous suspensions needed for such applications. Therefore, efforts have been made to modify the surface properties of such nanoparticles to be more compatible with aqueous media and thereby enhance the stability of aqueous suspensions of such nanoparticles. In some applications, it is also desirable that the nanoparticles have a relatively monodisperse particle size distribution. However, such surface treatments typically result in a relatively polydisperse particle size distribution.
Typically, nanoparticle compositions in aqueous suspension are subject to agglomeration and precipitation of the constituent nanoparticles. Surface treatments may be used to inhibit such agglomeration and precipitation, and may take the form of adding one or more stabilizer substances to a suspension of a nanoparticulate core species in a diluent. Such stabilizer substances are thought to attach to the surface of the suspended nanoparticulate core species and to form a barrier (or shell) interposed between at least a portion of the surface of the nanoparticulate core species and the diluent in which the nanoparticulate core species are suspended.
Formulations comprising nanoparticle compositions suitable for use in medical imaging applications typically require purification prior to presentation to a subject. The various purification techniques employed may degrade the hydrophilicity of the nanoparticle composition and may alter the particle size distribution of the nanoparticle composition. Prudent medical practice and logic strongly suggest that formulations containing nanoparticle compositions to be used as contrast agents for in vivo use in human subjects will be subjected to rigorous purification and be required to exhibit robust suspension stability in isotonic aqueous media, for example in 150 mM sodium chloride solution.
Thus, there is a need for nanoparticle compositions with improved properties, particularly related to increased hydrophilicity, stability in colloidal suspension, and enhanced safety.